In-Silico Cancer Research Published
October 14, 2010
School of Engineering, Coimbatore
They say that we wake up every day as a completely new person. At a cellular level, this is literally true, since trillions of cells in our bodies die every day and a whole horde of new cells are born in their place.
The findings of a multidisciplinary research team of the Computational Chemistry Group (CCG) at the Amrita Centre for Computational Engineering and Networking (CEN) underlining this idea were recently published in the international journal Information and Communication Technologies – Communications in Computer and Information Science (Springer).
The paper titled, Designing a Promotor for a Novel Target Site Identified in Caspases for Initiating Apoptosis in Cancer Cells elaborated on identifying the best ways to destroy and inhibit the growth of cancerous cells.
“Apoptosis is the mechanism by which nature eliminates old cells so that there is place for new ones,” explained Dr. Krishnan Namboori, who led the team. We can initiate apoptosis in cancerous cells so that nature can aid in the control of this disease.”
Dr. Krishnan further explained the methodology followed. “A deviation in the apoptotic pathway and the cells follow an uncontrollable growth pattern, resulting in what we know as cancer. Caspases is a key enzyme in the apoptotic pathway, the sequence of cells as they approach programmed death.”
Dr. Krishnan’s team performed in-silico drug design i.e. design of drugs through computer simulation. The team aimed to design a promotor substance that could activate the inactive caspases to set the apoptotic pathway right.
The task required detailed understanding of all the metabolites involved and their roles in the cellular pathway. “To know the pathway, one needed to know each and every metabolite involved,” emphasized Dr. Krishnan.
After the pathway was fully comprehended, the next step was to shortlist the ideal promotor from a list of 38 potential candidates. The 38 potential promoters selected, all with anti-carcinogenic properties, also included reported anti-cancer drugs.
Finally three compounds were identified as having the maximum effect in activating caspase proteins, thereby providing better chances for cancer therapy.
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The multidisciplinary research team consisted of Mala S. Kumar, K. L. Lainu, V. Aghila, Dhanya Purushothaman from the School of Biotechnology (Amritapuri) as well as Varun Gopal and Vrinda Harishankar from the School of Engineering (Coimbatore).
Mala S. Kumar, K. L. Lainu, V. Aghila, Dhanya Purushothaman, K. Varun Gopal, P. K. Krishnan Namboori and Vrinda Harishankar, Designing a Promotor for a Novel Target Site Identified in Caspases for Initiating Apoptosis in Cancer Cells, Information and Communication Technologies Communications in Computer and Information Science-Springer, 2010, Volume 101, Part 1, 62-67, DOI: 10.1007/978-3-642-15766-0_10.
Caspases are enzymes that can cleave other proteins and control normal and abnormal cell death. Cancer cells generally lack apoptosis. In this research work, a computational approach has been adopted to design a promotor that targets the inactivated caspases particularly Pro-caspase-3 or caspase-7, which are the effector caspases that cleave the downstream substrates like lamin-A, ICAD and PARP. Out of the 38 anti-carcinomic compounds selected for the analysis, some of them are found to have positive charged substituents similar to the known drug; PAC1, which cleaves the safety catch mode that blocks the IETD active site. Site specific interactions of the proteins with these ligands were performed. From the interaction analysis, it was found that 3 compounds; Choline, Glaziovine, Dasatinib can effectively target caspases and activate them. It has been suggested that these compounds favor the activation of the effector caspase proteins, thereby giving a better option in cancer therapy.